1. Technical Field
This invention relates to a method of effervescent formulation for the promotion of tyrosine or a tyrosine precursor solubility, absorption and accuracy of measure for oral supplementation and its use with vitamin, mineral and nutritional supplements.
2. Description of the Related Art
Tyrosine is the amino acid precursor for the synthesis of the neurotransmitters norepinephrine and dopamine. A number of studies have shown that stress-induced depletion of brain norepinephrine is associated with performance deficit. Tyrosine appears to have a positive impact on stress-induced performance degradation in humans.
Tyrosine is a large, neutral amino acid found in dietary proteins. It is also formed in the liver and, to a limited extent, in the brain from phenylalanine, an essential amino acid. The hydroxylation of phenylalanine by phenylalanine hydroxylase forms tyrosine which is the precursor for the biosynthesis of the catecholamine neurotransmitters dopamine and norepinephrine. The recommended daily intake of phenylalanine is 2.2 grams. Tyrosine is found in both animal and vegetable protein with the level of tyrosine found in human food varying widely. Thus the total daily intake of tyrosine by an individual would vary according to the combination of animal and vegetable protein ingested.
The fundamental structural units of proteins are .alpha.-amino-acids, about 20 of which participate prominently in protein formation. These building-block molecules contain at least one carboxyl group and one .alpha.-amino group, but differ in the structure of the remainder of the molecule. All except the simplest one, glycine, are capable of existing in both D and L configurations with respect to their .alpha.-carbon but proteins contain only the L-enantiomers. The actual protein molecule consists of long-chain polymers which may be looked upon as having resulted from condensation of the amino acids thus producing amide (commonly called peptide) linkages. The number of amino acid molecules so condensed varies widely among different proteins, ranging from perhaps as few as 30 up to tens of thousands. Proteins are thus macromolecules which differ primarily from each other in the number of amino acid residues present and in the sequence of these in the polymer chain.
A neurotransmitter (NT) is defined as a chemical that is selectively released from a nerve terminal by an action potential, interacts with a specific receptor on an adjacent structure, and elicits a specific physiologic response. Most NTs derive from amino acids (or related compounds such as choline). Certain neurons synthesize only one, neuron-specific NT, others have been shown to synthesize 2 neurons or more NTs. Some neurons modify amino acids to form the "amine" transmitters (e.g., norepinephrine, serotonin); others combine amino acids to form "peptide" transmitters (e.g., endorphins, enkephalins); and still other neurons use amino acids unchanged or synthesized as transmitters. A few NTs are not related to amino acids.
Dopamine (DA) is the NT of some peripheral nerve fibers and of many central neurons (e.g., substantia nigra, midbrain, hypothalamus). The amino acid tryosine is taken up by dopaminergic neurons, converted by the enzyme tyrosine hydroxylase to 3,4-dihydroxyphenylalanine (dopa), decarboxylated by the enzyme aromatic L-amino acid decarboxylase to DA, and stored in vesicles. After release, DA interacts with dopaminergic receptors and is then pumped back by active processes (re-uptake) into the prejunctional neurons. DA levels are held constant by changes in tyrosine hydroxylase activity and the enzyme monoamine oxidase (MAO), which is localized in nerve terminals and metabolizes dopamine. DA is metabolized to several metabolites, including specifically homovanillic acid.
Norepinephrine (NE) is the NT of most postganglionic sympathetic fibers and many central neurons (e.g., locus ceruleus, hypothalamus). NE synthesis, like that of DA, also starts with the precursor tyrosine but continues as DA is hydroxylated by dopamine-beta-hydroxylase to form NE, which is stored in vesicles. Upon release, NE interacts with adrenergic receptors. This action is terminated largely by the re-uptake of NE back into the prejunctional neurons. Tyrosine hydroxylase and MAO regulate intraneuronal NE levels. Metabolism of NE occurs via MAO and catechol-O-methyltransferase to inactive metabolites (e.g., normetanephrine, 3-methoxy-4-hydroxyphenylethylene glycol, 3-methoxy-4-hydroxymandelic acid).
One of the factors which limits the extent of resistance the individual can mount apparently is his capacity to produce and respond to the neurotransmitter norepinephrine (NE). Studies with both animals and humans reveal that stress causes a sharp increase in the brain's use of NE because NE tracts are those activated by stress. This surge in use of NE tends to deplete available supplies, and as neural stores decline, so does the capacity to continue normal levels of performance. That the loss of NE is the cause and not merely the correlate of stress-induced behavioral decrements is suggested by the finding that biochemical reduction of NE even in the absence of stress can cause a reduction in performance similar to that caused by stress alone.
Tyrosine must compete with all the other large neutral amino acids for transport across the blood brain barrier. Therefore, the ratio of tyrosine to its amino acid competitors determines its rate of entry into the brain. Once in the brain, more is converted into NE if the neural circuits which require NE are activated. In other words, when the organism is at rest, excess tyrosine is not converted into a larger reserve pool of NE. But when the individual is under stress, available tyrosine is converted into NE at a faster rate to replenish expended NE. If sufficient tyrosine is not available to replace that which is used, NE and performance continue to decline.
This dietary-biochemical-neural pathway suggests a novel approach to slowing stress-induced performance degradation. If stress uses NE and NE decline reduces the level of functioning and performance, NE levels and performance can be restored by additional amounts of NE's precursor tyrosine.
A tyrosine dietary supplement is a realistic alternative to increasing NE levels for slowing stress-induced performance degradation. L-tyrosine is the most commonly used tyrosine supplement for oral consumption, although other tyrosine salts, tyrosine isomers, and synthetic tyrosine formulations exist. L-tyrosine supplementation of 100 mg/kg to 150 mg/kg were the most commonly used dosages in human studies. These dosages created maximal increases that were seen for 2 hours after tyrosine ingestion, thereafter catecholamine levels returned to base line. Supplemental tyrosine (100 mg/kg) has, in fact, been shown to enhance mental performance, improve mood, and diminish symptoms in human subjects exposed to such stressors as cold and high altitude. To achieve desired effects dosages of 7 to 15 grams of L-tyrosine will need to be consumed 1 hour prior to competition or intense exercise.
The problem with existing tyrosine supplements is that accurate dosage is difficult to achieve. This is so because tyrosine does not dissolve well in water or other neutral pH liquids and is very acid liable. This results in irregular dosage, inconsistent results, and limited absorption due to stomach acid destruction.